Malaria is a group of diseases caused by hemosporidian blood parasites of the genus Plasmodium, transmitted by mosquitoes. After development in the host's liver, the parasites attack erythrocytes in the bloodstream. Development of the parasites in the erythrocytes, division and simultaneous bursting produce malarial attack.
Fetal hemoglobin inhibits the maturation of the malaria parasites, but after about four months, the human body's production of fetal hemoglobin is substantially decreased.
It is thus an object of the present invention to provide a method for preventing malaria by administering, butyrate analogs, activin or an activin-related peptide, to a subject at risk of being infected by the malaria-causing blood parasites, to increase fetal hemoglobin production.
Activin, a hormone, sometimes also referred to as erythroid differentiation factor (EDF) or follicle-stimulating hormone releasing protein (FRP), is a homodimer consisting of either two .beta..sub.A subunits of inhibin (Activin A), two .beta..sub.B subunits of inhibin (Activin B), or a subunit each of .beta..sub.A and .beta..sub.B (Activin AB). Inhibin is another hormone which, among other effects, suppresses secretion of FSH (follicle-stimulating hormone) from the pituitary gland. Inhibin is a protein consisting of .alpha. and .beta..sub.A subunits linked by disulfide bonds. Activin is present, in analogous forms, in mammals and have been reported, for instance, in human, porcine, and bovine follicular fluid. Porcine inhibin has been purified and sequenced from porcine follicular fluid as described in U.S. Pat. No. 4,740,587. The DNA encoding the prepro inhibin .alpha. and .beta. chains of porcine or human inhibin has been isolated, ligated into expression vectors and expressed in mammalian culture. See European Patent Application No. 222,491, published May 20, 1987. Activin A has been shown to induce hemoglobin accumulation in a human erythroleukaemic cell line and to induce the proliferation of erythroid progenitor cells in human bone marrow culture. See Yu, et al., Nature, 330, 765 (Dec. 24, 1987). The structures and isolation of activin have been reported by several groups in the literature. See Vale, et al., Nature, 321: 776 (1986); Ling, et al., Nature, 321: 779 (1986); Ito, et al., Biochem. Biophys. Res. Comm., 142, 1095 (1987); Tsuji, et al., Biotech. Bioeng., 31, 675 (1988); Shibata, et al., Biochem. Biophys. Res. Comm., 146, 187 (1987).